World population continues to increase at a frightening rate, particularly in developing countries. At the 1990 fertility rate (approximately 4 children per woman world-wide) there would be over 75 billion people on earth in the year 2100, compared to 6 billion at the present time. Even at the very optimistic projection of 2.5 children per woman, global population will grow to 19 billion by the year 2100. In addition, approximately one-quarter of all pregnancies are unwanted, leading to millions of abortions (1.5 million surgical or medical abortions annually in the United States) and approximately 100,000 deaths worldwide per year of otherwise healthy young women due to the complications of abortion. It is well established that men will use contraceptives (approximately 30% of all contraception in the U.S. now is accomplished with male methods). Therefore, the development of new, effective, safe, reversible male contraceptives is an extremely important societal goal. The work proposed in this application is designed to increase our basic and clinical knowledge of reproductive processes in the male with particular relevance to contraception. We are committed to excellence across the spectrum of studies proposed, from basic molecular biology and biochemistry through human physiology with direct application to contraceptive development. We have four research projects: 1) hormonal contraceptive studies in men (Dr. W. Bremner, PI), 2) genetic studies of the control of spermatogenesis in mice (Dr. R. Braun, PL), 3) studies of the roles of phosphodiesterases and their inhibitors in the testis (Dr. J. Beavo, PL), and 4) the cell-specific patterns of gene expression and their control in the testis (Dr. M. Griswold, PL). We also propose a Program for Fellows and New Investigators in Male Contraception and an Administration Core Unit. Our proposal incorporates the talents of outstanding investigators of varied backgrounds and professional training into an interactive research program in reproductive biology. We have structured this Center to meld superb science with the practical goal of applying new basic knowledge as quickly as possible to studies in human beings. We hope that, in this way, our work will address critical needs of society.